Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
PEDPACK: USER'S MANUAL by AlUD Thomas TECHNICAL REPORT No. 99 July 1987 Department of Statistics, GN-22 University of Washington searae, Wa~ihinl~ton 98195 USA PEDPACK: USER'S MANUAL AlunThomas ABSTRACT Pedpack is a package of programs for pedigree analysis which uses the UNIX operating system. The programs are written in C. This manual is intended for users familiar with the UNIX commands and file handling system but not necessarily with programming. Fonowing a description of the programs provided by Pedpack, the transcripts of three.demonstration sessions are given. These cover basic.pedigree management, drawing pedigrees and calculation of probability functions. There is also a bibliography relevant to those aspects of pedigree analysis covered by the package. The development of PEDPACK and production of this report were supported in part by a grant entitled "Pedigree Analysis in Genetic Isolates" to Elizabeth Thompson, from the Graduate S«;hOQIResear«;h Fund of the University of Washington. Table of Contents 1. Introduction to Pedpack 1 2. Main pedigree handling commands provided by Pedpack 1 3. Description of all commands provided by Pedpack 2 4. Demonstration 1: Basic pedigree management 8 5. Demonstration 2: Drawing the pedigree 19 6. Demonstration 3: Peeling 23 7. Bibliography 29 1. Introduction to Pedpack. Pedpack is a set of programs for creating, managing and analysing databases for pedigrees and genetic traits. It runs under the UNIX operating system and the user requires familiarity with the basic UNIX file structure and command language. When called for the first time the command Pedpack creates a directory called Ped,work and takes the user into this directory. Future calls from the same directory move the user into the already existing Ped.work, A C shell is entered and the pedigree handling programs are made available. The default prompt inside Pedpack is a question mark-? Standard UNIX commands should also be available, except for cd which is disenabled to prevent the user from leaving directory Ped. work until Pedpack is exited completely using either quit or exit. Once inside Pedpackthere should be no need to move to other directories. Two subdirectories called Pedigreea and Traits are created in Ped.work, these will contain the pedigree and genetic trait databases. While files in Ped.work itself can be safely moved, edited etc. using the usual UNIXcommands those in Pedigrees and Traits should be created and changed only through the commands provided by Pedpack, Users can edit the .cshrc file in Ped, work to make aliases or to modify the path so that their own commands can also be available in Pedpack, Upon typing quit or exit the Pedpack C shell is exited and the user is returned to the directory from which Pedpack was originally called. Any databases or output files created during the session remain in Ped.work or its subdirectories and will be available when Pedpack is next called. The command help can be used from inside Pedpack for more information about the package. 2. Main pedigree handling commandS provided by Pedpack. newped Takes a raw pedigree, specified in standard triplet form and creates a database for use by subsequent programs. newtrait Creates a database representing the structure of a genetic trait. getgendat Gets genetic data about a pedigree from an input and incorporates this into the pedigree database. checkgendat on a peoigree -2- • with Mendelian segregation. browse Allows the user to inquire about the structure of and the genetic data on a pedigree. This includes calculation of inbreeding and kinship coefficients and enumeration of relationships between individuals. update Allows the user to add new individuals to a pedigree and to alter data already present. setcoords & draw Used together these produce a drawing of the pedigree as a marriage node graph. Simulated annealing is used to optimise the clarity ofthe picture. Uses the peeling method to calculate probability functions for genetic data on simple or complex pedigrees. This command includes options to generate random peeling sequences and to improve the efficiency of sequences using simulated annealing. peel A fuller description of these programs and all the other Pedpack commands are given in the following section.. 3. Description of all commands provided by Pedpack, 3.1. browse Brings a pedigree on line and allows the user to inspect various aspects of it. Available options are inf infx all inb x inb all inb pro prints prints prints prints prints prints x information about the pedigree information about individual x information about each individuals in the pedigree the inbreeding coefficient of x all the inbreeding coefficients for the pedigree a of by generation generation x kinship coerncient of x y quit (q) prints all the relationships between x and y leaves browse and returns to Pedpack Output from browse can be redirected using >. For example: ? browse Bison »outfile n inf 123 n inb all nq ? This prints information about Bison 123 and aU the inbreeding coefficients for this pedigree into the file called outfile. 3.2. checkgendat Checks the data for the given trait on the given pedigree. Coding errors and segregation errors in nuclear families are looked for. This command should be used after inputting genetic data using either getgendat or update. For example: 't checkgendat ABO Samaritans 3.3. commands Gives a list of available commands. 3.4. draw Takes a pedigree with precalculated coordinates and produces a standard device independent plot file containing a marriage node graph picture of the pedigree. The file that the plot instructions are sent to must be the standard output file. If this is not specified using > then draw will try to put the picture on the screen immediately, causing nasty errors. An example of a set of commands for drawing a pedigree might be as follows: ? setcoords 1 plot outplot Where ... appears above the commands will prompt the user for required options. The plot command is a standard unix command, and output from it can be redirected from the screen to a hardcopy output device. 3.5. getgendat The user isproIIlPtedforthename of the file where genetic data for a pedi~ree is held. The columns of the filewheJ:"e thed,ata fora particular trait appear are then asked for along with the coding system used, i.e, which integer refers to which phenotype. The command checkgendat should be used after inputting genetic data. For example: 1 getgendat Rh Tristan 1 checkgendat Rh Tristan »outchecks 3.6. help Gives the following information: For a brief introduction to Pedpack type spec intro or just intro. For a list of the main pedigree handling programs type spec list. For a list of all available commands type commands. For a description of a command type spec followed by the name of the command. For a list of C subroutines by the package type subs. For a description of a subroutine type spec followed by the name of the subroutine. For information about installing Pedpack spec 11l;:)1i4ll. Calculates linkage disequilibrium for two loci each with two co-dominant alleles. 3.8. newped This program interrogates the user for the location of a new pedigree, and the name by which the pedigree is to be known. The pedigree is then read in and the structure set up. Some calculations are made to determine characteristics of the pedigree and it is then output, in a standard form, to the file Ped,work/Pedigreesz''name", where "name" is the identifier for the pedigree for future use. It is assumed that the pedigree is in the standard triplet form of name, father's name, mother's name and thai it satisfies the usual rules for specifying a pedigree, i.e. (1) One line of input must correspond to one individual. On each line the names of the individual and its parents must appear before any other data, and must be separated by spaces. (2) Names of individuals are positive integers while 0 is used to represent the unknown parents of founders. (3) All founders must be listed. For each individual who is not a founder both parents must be listed. (4) An individual always appears later in the list than its parents. 3.9. newtrait Sets up a new genetic trait for future reference. Each trait is set up independently of any pedigree. When prompted the user must input the number of alleles for the trait and the names. Then the number of phenotypes and their names are inputted. The program will then prompt the user for the penetrance matrix. There is a final option to delete the trait if mistakes have been made in inputting the parameters. -63.10. parameters Outputs the penetrance and Mendelian segregation probabilities, for any trait that has already been set up, to the standard output file. 3.11. peds Gives a list of the pedigrees that have been set up. 3.12. peel Uses the peeling method to calculate probability functions for genetic data on a pedigree. Most of the output from this program can be re-routed using >. Some will always go to the standard error file. Warning: this is a large number crunching program and should only be used when sensible peeling sequences are available. If you don't know what a peeling sequence is then you should not use this program. If c is the size of the largest cutset in the sequence and g is the number of genotypes then the program should run on pollux if: g C < 1,600,000 The peeling sequence used is originally set to be the order of marriages on the stack. There are, however, options to randomise this order and to improve the computational efficiency of the sequence using simulated annealing. 3.13. setcoords Sets up the pedigree with coordinates suitable for drawing a marriage node graph. There is an option to user annealing to clarify the picture by attempting to minimise the total squared line length of the picture. See draw for an example of how setcoords might be used. 3.14. spec Gives a brief description of the keyword following it. For example ? spec browse -7- 3.15. Gives a list of the traits that have been set up. 3.16. update Brings a pedigree on line and allows the user to update parts of it. Available options are inf infx add x altx new quit (q) prints information about the pedigree prints information about individual x adds individual x to the pedigree alters the data for individual x appends data from a new file to the original pedigree. leaves update and returns to Pedpack There is an option to overwrite the original pedigree or to create a new one. The command checkgendat should be used whenever update has been used to change any genetic data. 4. Demonstration 1: Basic pedigree management. following is a transcript of a session, using Pedpack,which demonstrates how new pedigree and trait databas.esare created and updated. help and spec commands are given, and Is is used to show subdirecrories Pedigrees and Traits. user would type those words following the prompts %, ?, nor ... fV\lJ""q&. Pedpack Creating a working directory called Ped.work for pedigree analysis. Two subdirectories called Pedigrees and Traits are created in reU.worK. these will containrhepedigree and genetic trait databases. Ped.work itself c8n.he. safely moved, edited etc. using the commands those in Pedigrees and Traits should be created only throughthe commands provided by Pedpack, Users can edit the .cshrc file in Ped.work to make aliases or to modify the path so that their owncommands can also be available inPedpack. Upon typing quit or exit the Pedpack C shell is exited and the user is returned to the directory from which Pedpack was originally called. Any databases or outputfiles created during the session remain in Ped.work or its subdirectories and will be available when Pedpack is next called. Directory Ped.work created. Introduction to Pedpack. The command help can be used from inside Pedpack for more information about the package. ? Is is a set of programs for creating, managing and analysing pedigrees and genetic traits. It runs under the UNIXoperating user requires familiarity with the basic UNIX file structure command language. for the first time the command Pedpackcreates a directory 'CU.work and takes the user into this directory. Future calls from the same move the user into the already existing Ped,work A C shell is and the pedigree handling programs are made available. The default promptinside Pedpack is a question mark-? Standard UNIX commands should also be available, except for cd which is to prevent the user from leaving directory Ped.work until Pedpaek is exited completely using either quit or exit. Once inside Pedpack be no need to move to other directories. Pedigrees Traits ?help For a brief introduction to Pedpack type spec intro or just intro. For a list of the main pedigree handling programs type spec list. For a list of all available commands type commands. For a description ofa command type spec followed by the command. For a list of C subroutines used by the package type subs. of the I 00 I a of a subroutine type spec followed by the name of the browse Allowsthe user to inquire about the structureof and genetic data on a pedigree. This includescalculation inbreeding and kinship coefficients relationships between individuals. update Allowsthe user to add new individuals to a pedigree to alter data already present. infonnation about installing Pedpack type spec install. Pedpaek type quit. ?commands setcoords & draw vailable commands: draw peds intro newtrait setcoords triplets checkgendat updatecommands getgendat parameters spec newped peel subs doublepeel help peel '] Used together these produce a drawing of the pedigree as a marriage node graph. Simulated annealing is used optimise the clarityof the picture. Uses the peeling method to calculateprobability functions for geneticdata on simple or complex pedigrees. This command includesoptions to generate random peeling sequences and to improve the efficiency of sequences using simulated annealing. pedigree handling commands provided by Pedpack, ? spec newped newped Takes a raw pedigree, specified in standard triplet form and creates a database for use by subsequent programs. Createsa database representing the structure of a genetic trait. Gets geneticdata abouta pedigree from an input file and incorporates this into the pedigree database. Checks geneticdata on a pedigree for codingerrors and for genotypes on nuclearfamilies inconsistent with Mendelian segregation. SPEC: newped This program interrogates the user for the location of a new pedigree, and the name by whichthe pedigree is to be known. The pedigree is then read in and the structure set up. Some calculations are made to determine characteristics of the pedigree and it is then output, ina standard form, to the file Ped.work/Pedigreesr'name", where "name" is the identifier for the pedigree for future use. It is assumed that the pedigree is in the standard triplet form of name, \0 name, mother's name and that it satisfies the usual rules for Pedigree Test has been set up, 23 individuals inputted. seecifvins a pedigree, i.e, ? spec browse (I) One line of input must correspond to one individual. On each names of the individual and its parentajmust appear other data, and must be separated by spaces. (2) Names of individuals are positive integers while 0 is used to SPEC: browse Brings a pedigree on line and allows the user to inspect various aspects it represent the unknown parents of founders. Available options are All founders must be listed. For each individual who is not a founder both parents must be listed. An individual always appears later in the list than its parents. '/ cp /pol.lux/pedpacklPedigreesffestitriplets triplets '?Is triplets inf inf x inf all inb x inb all inb pro inb gen x kin x y rel x y quit (q) : prints information about the pedigree : prints information about individual x : prints information about each individuals in the pedigree : prints the inbreeding coefficient of x : prints all the inbreeding coefficients for the pedigree : prints a profile of inbreeding by generation : prints aUthe inbreeding coefficients for generation x : prints the kinship coefficient of x and y : prints all the relationships between x and y : leaves browse and returns to Pedpack '/ Output from browse can be redirected using >. r'nrrpntlu existing pedigrees E.g. '/ newped ? browse Bison >outfile program reads in a new pedigree specified in standard triplet form. name of the file that the pedigree is in ... triplets ?? inf 123 n inb all name of the pedigree ... Test ??q I ..... o I Inbreeding(l) ? information about Bison 123 and all the inbreeding coefficients pedlign~e into the file called outfile, 0.00000 ?? kin 1 2 Kinship(I,2) = 0.00000 ?browse ??q ?peds :I Pm,.",ntll : °° Spouse: 5 Children: 9 : female Generation : 1 JJejl:ree: 1 Inbr,eedi:ng : 0.00000 Coordinates : (0,00000,0.00000) 6 :6 Parents: Spouse : 14 Children: 16 Spouse: 9 Children: 15 13 12 10 : female Generation : 1 1,JCl:&U;;;C: 2 Inb£1eedlll1g : 0.00000 Cocrdiaates : (0.00000,0.00000) °° Currently existing pedigrees Test ? spec newtrait I l-' l-' SPEC: newtrait Sets up a new genetic trait for future reference. Each trait independently of any pedigree. When prompted the. user must number of alleles for the trait and the names. Then the number phenotypes and their names are inputted. The program will then prompt user for the penetrancematrix. There is a final option to delete the trait if mistakes have been made inputting the parameters. ? traits Currently set up traits ? newtrait I of ... MN Check the penetrancematrix. m mn n MM 1.000000.00000 0.00000 MN 0.00000 1.00000 0.00000 NN 0.000000.000001.00000 ;:semng up genetictrait MN. alleles ... 2 Number of phenotypes ... 3 Unless you type no this trait will be installed ... y names when prompted. ? traits 1 ... M Currently set up traits 2 ... N MN pbenotype names when prompted. ? spec parameters Phenotype I ... m SPEC: parameters Phenotype 2 ... mn Phenotvoe 3 ... n penetrance probabilities, one genotype ata time m mn n MM 1 0 0 m mn n MN 0 1 1 m mn n 010 m mn n 001 Outputs the penetranee and Mendelian segregation probabilities. for any trait that has already been set up, to the standard output file. ? parametersMN Number of alleles 2, namelyi- M N Numberof genotypes 3 Numberof phenotypes 3 Penetrancematrix: Phenotypes Genotypes unknown m mn n MM 1.00 1.00 0.00 0.00 MN 1.00 0.00 1.00 0.00 ..... N I 1.00 0.00 0.00 1.00 Segreganon matricies: genotype: MM MM MN NN MM 1.00 0.50 0.00 MN 0.50 0.25 0.00 0.00 0.00 aenotvre: MN MM MN NN MM 0.00 0.50 1.00 MN 0.50 0.50 0.50 1.00 0.50 0.00 genl()type: NN MN NN 0.00 0.00 0.00 0.25 0.50 0.00 0.50 1.00 ? getgendat [Using open mode] "input" [New file] 12 22 31 43 121 :wq "input" [New file] 5 lines, 25 characters ? Is Pedigrees Traits I input triplets ? getgendat Name oftrait .,. MN Name of pedigree ... Test Type full name of input file ... input user is prompted for the name of the file where genetic data for a eediaree is held. The columns of the file where the data for a particular trait are then asked for along with the coding system used, i.e, which to whichphenotype. Ready to input data for MN. Data for individuals must be on separate lines in the file. When prompted give the column numbers where the data items named are listed. command checkgendat should be used after inputting genetic data. First column of name ... 1 ? vi ..... w Checks the data for the given trait on the given pedigree. Coding errors and segregation errors in nuclear families are looked for. column of name ,.. 2 column of genetic data ... 4 column of genetic data ... 4 is the largest code number for a phenotype? ... 3 numbers for each of the phenotypes. This command should be used after inputting genetic data using either getgendat or update. ? checkgendat MN Test Checking data for trait MN on pedigree Test. Phenotype m ... 1 Checking individual data for coding errors. No coding errors. Phenotvoe mn ... 2 Phenotvoe n ... 3 Type! to overwrite Test or give a new pedigree name .... ! Observed phenotype frequencies. unknown 18 m 2 mn 2 n 1 Finding allele, genotype and phenotype frequencies. ? Is EM algorithm converged to an accuracy of O.OooOOe+OO in 1 iterations for 5 individuals were considered, 5 items were input and 0 were input ? Currently ? triplets Alleles. M N Frequency 0.60000 0.40000 pedigrees Genotypes. M M 0.36000 M N 0.48000 N N 0.16000 Phenotypes Std. error 0.15492 0.15492 I-' .j:-. I Observed Expected Chi-sqd 2 1.800 0.02222 m 2 2.400 0.06667 mn 1 0.800 0.05000 n 5 5.000 0.13889 on 1 degrees offreedom. nuclearfamily for segregation errors. segregaaon errors found. ? Pedigreedata for Test :Number ofindividuals "" 23 Number of marriages"" 12 Number of indlists 16 Number ofll1arlists == 24 Highestlabel == 23 Number of components I Highestgenerati'on "" 5 Coordinatestset== NO Generations reset == NO Inbreeding calculated == YES Numberofgenetic traits set 1 namely: MN. ?? inf 1 a pe(Uf!ree on line and allows the user to update parts of it. vailable options are x new information about the pedigree information about individual x ; aces individual x to the pedigree the data for individual x : appends data from a new file to the original pedigree. : leavesupdate and returns to Pedpack is an codon to overwrite the original pedigreeor to create a new one. command checkgendat should be used wheneverupdate has been used to chanae anv geneticdata. '1 Pedigree data.- ' Name: 1 Parents: 00 Spouse: 5 •Children: 9 Sex: female Generation: 1 Degree: 1 Inbreeding: 0.00000 Coordinates: (0.00000,0.00000) Genetic dara.MN:2 ?? inf6 Pedigreedata.Name: 6 °° Parents: Spouse: 14 Children: 16 Spouse: 9 Children: 15 13 12 10 : female Generation: 1 Degree: 2 Inbreeding: 0.00000 Coordinates : (0.00000,0.00000) ?? add 24 Give names of parents, father ... 22 mother ... 23 MN:O O.K., 24 with parents 22 and 23 added. 6 ?? inf24 J"\nta IUl; individual 6. Coordinates of 6 are (0.00000,0.00000). or C to change ... ! Type ! to phenotypic data is not checked at this stage. MN is phenotype number O. it or C to change ... C phenotype number ... 3 6 Pedigree datatName: 24 Parents: 22 23 Sex: unknown Generation : 6 Degree: 1 Inbreeding: 0.31250 Coordinates: (0.00000,0.00000) Genetic dataiMN:O ?? alt 24 :6 P!:Irl'nt" : 00 Spouse: 14 Children: 16 Spouse : 9 Children: 15 13 12 10 Sex: female Generation : 1 ~J<;;;CU;;V: 2 Inbreeding: 0.00000 Coordinates : (0.00000,0.00000) Altering individual 24. Sex of 24 is unknown. Type! to leave it and M,F or U to change it ... M Coordinates of 24 are (0.00000,0.00000). Type ! to leave them or C to change .., ! Warning: altered phenotypic data is not checked at this stage. Data for trait MN is phenotype number O. Type! to leave it or C to change ... C phenotype number ... 2 m mn n 2 3 2 Finding allele, genotype and phenotype frequencies. PedifUl::e datat: 24 Parents : 23 : male Generation: 6 JJI;¢~:;U;;I;¢: 1 Inbreeding : 0.31250 Coerdmates : (0.00000,0.00000) :2 EM algorithm converged to an accuracy of O.OOOOOe+OO in 0 iterations Alleles. M N Frequency 0.50000 0.50000 Std. error 0.13363 0.13363 Genotypes. M M 0.25000 M N 0.50000 N N 0.25000 q I-' "'-J individuals added» 1. Number of individuals altered == 2. Phenotypes Observed Expected Chi-sqd m 2 1.750 0.03571 mn 3 3.500 0.07143 n 2 1.750 0.03571 ! to overwriteTest or name a new pedigree.... ! Total ? 7.000 0.14286 on 1 degrees of freedom. MNTest for trait MN on pedigree Test. Cb::cking individual data for coding errors. errors. OhllP:rvPtf 7 phenotype frequencies. 17 Checking each nuclear family for segregationerrors. Parents 9 and 6 with phenotypes 0 3 with children name 15 type 0 name 13 type 0 name 12 type 1 name 10 type 0 Errors found in 1 families. Checking individual data for codingerrors. No codingerrors. ? tupdate 12 _ individual 12. of 12 is unknown. ! to it and M,For U to changeit ... ! Coordinates of 12 are (0.00000,0.00000). them or C to change ... ! Observed phenotype frequencies. unknown 17 m 1 mn 3 n 3 Findingallele, genotype and phenotype frequencies. EM algorithm converged to an accuracy of O.OOOOOe+OO in 1 iterations Alleles. phenotypic data is not checked at this stage. MN is phenotype number 1. it or C to change ... C Frequency Std. error 0.35714 0.64286 0.12806 0.12806 M N I I-' 00 phenotype number... 3 Genotypes. M M 0.12755 M N 0.45918 N N 0.41327 q Number individuals added = O. Number individuals altered == 1. Type! to overwrite Test or name a new pedigree. Phenotypes Observed Expected Chi-sqd m 1 0.8930.01286 mn 3 3.2140.01429 n ? Total ctleclCg.enaat MNTest 3 2.893 0.00397 7 7.000 0.03111 on 1 degreesof freedom. Checking each nuclearfamily for segregation errors. No segregation errorsfound. for trait MNon pedigree Test. ? browse Test »alldata 22 21 20 1 50.31250 0 23 21 18 2 50.18750 0 24 22 23 1 60.31250 2 q ? Is ? quit alldata input triplets ?poHux% ?more S. Demonstration 2: Drawing the pedigree. of lJedijtUee Test. name pa ma sex gen inb-cf traits 1 0 0 2 10.00000 2 2 0 0 2 10.00000 2 3 0 0 1 10.00000 1 4 0 0 1 10.00000 3 5 0 0 1 10.00000 0 6 0 0 2 10.00000 3 7 0 0 2 10.00000 0 8 4 7 2 20.00000 0 9 5 1 1 2 0.00000 0 10 9 6 1 30.00000 0 11 5 8 2 3 0.00000 0 9 6 0 3 0.00000 3 13 9 6 2 3 0.00000 0 14 5 8 1 3 0.00000 0 9 6 2 3 0.00000 0 14 6 0 40.00000 0 10 2 0 40.00000 0 3 2 40.00000 0 19 9 11 0 4 0.12500 0 10 13 2 40.25000 0 10 1 40.25000 0 In this session transcript the pedpack commands setcoords and draw are used in conjunction with the standard unix command pIotto produce a marriage node-graph of the pedigree set up in demonstration 1. The marriage nodegraphproduced is shownat the end of this section. I-' \0 pollux% Pedpack Directory Ped, workentered ?peds Currently existing pedigrees Test ? specsetcoords SPEC: setcoords Sets up the pedigree with coordinates suitable for drawing a marriage node graph. There is an. option to user annealing to clarify the piqture by attempting to minimise the total squared line lengthof the picture. for an example of how setcoords might be used. ? Resetting generations. New coordinates have been calculated for Test. Do you wish torrse.armealing to improve the picture? (yIn) ... y Using the annealing algorithm to minimise total squared line length. To fix marriagesatsofile generations type f ... f a with precalculated coordinates and produces a standard independent plot file containing a marriage node graph picture of the plot instructions are sent to must be the standard output is not specified using :> then draw will try to put the picture on screen immediatelv, causing nasty errors. Type number of generation to be fixed. Type quit or q when finished first ... 3 next ... q Number of iterations ... 10000 An examole of a set of commands for drawing a pedigree might be as Starting temperature ... 1 N o '1 seteoorcs I Cooling factor ....99 Searching for a minimum total squared line length graph »ourplot ? Total squared x distances at start Starting temperature Cooling factor 1.05286 1.00000 0.99000 ? appears above the commands will prompt the user for required command plot is a standard unix command, and output from it can be the screen to a hardcopy output device. ? setcooros Total squared x distances after searching0.26651 Finishing temperature "" 0.00000 Freezing temperature 0.00527 "" 10000 Number of tries "" 149 Number of downhill steps "" 683 Last downhill step 130 Number of uphill steps == 523 Last uphill step steps step 5 332 10.120 ! to overwrite Test or name a newpedigree.. '1 Is alldata input ? draw triplets »picnire Do vou wanta frame? (yin) ... y want labels? (yin) ... y graphof pedigree drawn to standard outputfile. ? ? ?nnllmc% - 225.1. Marriage node graph attest pedigree. 6. Demonstration 3: Peeling. Nameof trait .,. MN session transcript we use the pedigree and trait set up in demonstration 1 to demonstrate the use of the peeling program. Nameof pedigree ... Test Peeling data for trait MN on pedigree Test. Directory Ped.work entered '! Type namesof individuals in reference set. Type quit or q when finished. first ... 3 next ... 5 peeling method to calculate probability functions for genetic data on a pedigree, next ... q of the output from this program can be re-routed using >. Some will to the standard error file. Warning: this is a large number crunching program and should only he used sensib'le peeling sequences are available. If you don't know what a peeling is thenyou should not use this program. If cis of the largest cutset in the sequence and g is the number of the program shouldrnn if: g**c < 2,000,000 pe~lJil1lg sequence used is originally set to he the order of marriages on There are, however, options to randomise this order and to computational efficiency of the sequence using simulated ? next ... 22 N W Peelingorder is beingset to order of marriages in stack. Largestcutset cost for this sequence is 8.000. Do you want to improve the sequence? (yin) ... y Type: ann to anneal the sequence, ran to randomise the sequence, use to use the currentsequence for peeling, q to dump the sequence and quit peel altogether. ann, ran, use or q ... ann Using simulated annealing to improve the peeling sequence. When prompted input the annealing parameters. Number of iterations ... 10000 Starting temperature Cooling n •• .n 10 ? Is Pedigrees alldata 99 Traits input outlikes picture outpeel triplets cutset cost is 5.000000 ? more outpeel ann, ran, use or q n. use Using simulated annealing to improve the peeling sequence. Total: 450000e+00 18 Total: 1.35000e+Ol \.-UU>CL. 3 1521 22 Total: 1.72194e+00 101521322 Total: 1.72194e+00 LmSCI.: 20 10 153 Total: 1.43495e+00 153 Total: 6.58905e-Ol 13 153 Total: 6.25960e-Ol \"'U'bI;;;,; 9 6 3 Total: 1.09611e-02 Cutset: 9 11 6 3 Total: 3.29032e-02 \.-Ulbca; 5 11 6 3 Total: 6.06578e-03 145 11 3 Total: 1.81973e-02 \"'U'bti,; 5 8 3 Total: 6.06578e-03 \.-UI2'lCI. 5 3 Total: 8.35592e-04 Order of 3 individuals in final cutset is: 5 3 Number of iterations 10000 Starting temperature 10.000000 Cooling factor 0.990000 Maximum storage at start 8.000000 Starting time 0.240000 Maximum storage at end Number of uphill steps Last uphill step Freezing temperature Number of lateral steps Last lateral step Number of downhill steps Last downhill step Stopping time 5.000000 121 632 0.017612 805 9999 308 9982 18.339996 19.000 seconds. likelihood has 27 terms. Type name of output file for likelihoods or type ! to dump result. r\ name or ! n. outlikes l:._ Outputting result to outlikes, Checking individual data for coding errors. No coding errors. Observed phenotype frequencies. unknown 17 1 m N .p- I mn n Time used for this operation: genotype and phenotype frequencies. Peeling marriageof21 and 18 with children: 23 Segregation for 23 R function for 22 23 Numberof individuals involved is 4 Numbersummed out is I, namely: 23 Numberin output cutset is 3, namely: 21 18 22 Number of terms in output cutset is 27 Number of non-zerocontributions: 37 Numberof non-zeroterms : 25 Total likelihood : 1.35000e+01 Time used for this operation: 0.020 seconds. 3 algorithm converged to an accuracy of O.OOOOOe+OO in 1 iterations M N M Frequency 0.35714 0.64286 Std. error 0.12806 0.12806 M 0.12755 M N 0.45918 N N 0.41327 m mn n Expected Chi-sqd 1 0.893 0.01286 3 3.214 0.01429 3 2.893 0.00397 7 7.000 0.03111 on 1 degrees of'freedom. of 22 and 23 with children: 24 24 24 individuals involved is 3 Number summed out is I, namely: 24 Number in outputcutset is 2, namely: 22 23 terms in outputcutset is 9 non-zero contributions : 7 non-zero terms :7 : 4.50000e+00 J)",,,,lino 0.020 seconds. 3 Peeling marriage of3 and 15 with children: 18 Penetrance for 3 Segregation for 18 Prior for 3 R function for 21 18 22 Numberof individuals involvedis 5 Numbersummed out is I, namely: 18 Numberin output cutset is 4, namely: 3 1521 22 Numberof terms in output cutset is 81 Numberof non-zerocontributions: 34 Numberof non-zero terms : 26 Totallikelihood: 1.72194e+00 Time used for this operation: 0.020 seconds. Peeling marriageof 10 and 15 with children: 21 Indexfor 3 Segregation for 21 R function for 3 15 21 22 Number of individuals involved is 5 Number summed out is 0, namely: N VI cutset is 5, namely: 10 15 21 3 22 terms in output cutset is 243 Number of non-zero contributions: 43 : 43 Number of non-zerc terms likelihood: I.72194e+00 0.040 seconds. this operation: P~~1ina of 21 and 20 with children: 22 3 Segreganon for R function 10 1521 3 individuals involved is 6 Number summed out is 1, namely: 21 output cutset is 5, namely: 2022 10 153 terms in output cutset is 243 Number of aon-aero contributions : 77 Number of non-zero terms : 55 : 1.43495e+00 this operation: 0.080 seconds. Peelinc marriage of 10 and 2 with children: 17 2 Seglregation for 17 2 R function for 2022 10 153 individuals involved is 7 Number summed out is 2, namely: 2 17 cutset is 5, namely: 10 20 22 153 Number of terms in output cutset is 243 non-zero contributions : 131 non-zero terms : 55 Total likelihood : 6.58905e-Ol used for this operation: 0.120 seconds. Peeling marriage of 10 and 13 with children: 20 Index for 3 Segregation for 20 R function for 10 20 22153 Number ofilldividuals involved is 6 Number summed out is I, namely: 20 Number in output cutset is 5, namely: 101322153 Number of terms in output cutset is 243 Number of non-zero contributions: 99 : 66 Number of non-zero terms Total likelihood : ·6.25960e~01 Time used for this operation: 0.080 seconds. Peeling marriage of 9 and 6 with children: 15 13 12 10 Penetrance for 6 Penetrance for 12 Index for 3 Segregation for 15 Segregation for 13 Segregation for 12 Segregation for 10 Prior for 6 R function for 10 1322153 Number of individuals involved is 8 Number summed out is 4, namely: 15 13 12 10 Number in oUlput cutsetis 4, namely: 9 6 22 3 Number of termsinoutput cutset is 81 Number of non-zero contributions: 21 Number of non-zero terms :4 Total likelihood : I.09677e~02 Time used for this operation: 0.020 seconds. Peeling marriage of 9 and 11 with children: 19 Index for 6 tv 0' I Index for 3 Segregation for 19 R function for 9 6 22 3 Number of individuals involved is 6 Number summed out is I, namely: 19 Number in output cutset is 5, namely: 9 II 6 22 3 Number of terms in output cutset is 243 non-zero contributions : 25 Number of non-zero terms : 12 : 3.29032e-02 this operation: 0.040 seconds. Peeling marriage of.5 and 1 with children: 9 I Segregation for 9 5 1 R function for 9 11 6 22 3 individuals involved is 7 Number summed out is 2, namely: 1 9 Number in output cutset is 5, namely: 5 11 6 22 3 terms in output cutset is 243 Number of non-zero contributions: 33 non-zero terms : 27 : 6.06578e-03 this operation: 0.060 seconds. Peeling marriage of 14 and 6 with children: 16 Index for 6 Index for 3 Segregation for 16 R function for 5 11 6 22 3 Number of individuals involved is 7 Number summed out is 2, namely: 6 16 Number in output cutset is 5, namely: 145 11 22 3 Number of termsin output cutset is 243 Number of non-zero contributions : 108 : 81 Number of non-zero terms Total likelihood : 1.81973e-02 Time used for this operation: 0.060 seconds. Peeling marriage of 5 and 8 with children: 14 11 Index for 3 Segregation for 14 Segregation for 11 R function for 145 11 223 Number of individuals involved is 6 Number summed out is 2, namely: 14 11 Number in output cutset is 4, namely: 5 8 22 3 Number of terms in output cutset is 81 Number of non-zero contributions: 87 Number of non-zero terms : 27 Total likelihood : 6.06578e-03 0.040 seconds. Time used for this operation: Peeling marriage of 4 and 7 with children: 8 Penetrance for 4 Index for 3 Segregation for 8 Prior for 4 Prior for 7 R function for 5 8 22 3 Number of individuals involved is 6 Number summed out is 3, namely: 47 8 Number in output cutset is 3, namely: 5 22 3 Number of terms in output cutset is 27 N ""-.J non-zero contributions: 36 non-zero terms :9 likelihood: 8.35592e-04 thisoperation: 0.040 seconds. taken: 19.000 seconds. ? more outlises O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO I:lO.,oe- O.OOOOOe+OO 3.3:i98ioe-()4 O.OOOOOe+OO 51740e-05 3.0'166:Ze-{)S 1.39iQ2ge-05 >.06262Ie-05 14Yl:Se-IJQ • L.U'''-U.J 1U:l ? '1 O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO O.OOOOOe+OO N 00 I - 297. Bibliograpby. 7.1. General. Cavalli-Sforza, L.L. & Bodmer, W.F. 1971. The Genetics ofHuman Populations. W.H. Freeman and Company, San Francisco. Thompsen, E.A. 1986. Pedigree Analysis in Human Genetics. The Johns Hopkins University Press. Mourant, A.E., Kopec, A.C., & Domaniewska-Sobczak, K. 1976. The Distribution of the Human Blood Groups and other polymorphisms. Oxford University Press, London. 7.2. Programming. Kennedy,W..J. & Gentle, J.E. 1980 Statistical computing. New York: M. Dekker. Kernighan, B.W. & Pike, R. 1984. The UNIX programming environment. Englewood Cliffs, N.J.: Prentice-HalL Kernighan, B.W. & Richie, D.M. 1978. The C programming language. Englewood Cliffs, N.J.: Prentice-Hall. 7.3. Inbreeding. Darlington, C.D. 1960. Cousin marriages and the evolution of the breeding system in man. Heredity. 14,297-332. Hajnal, J. 1963. Random mating and the frequency of consanguineous marriages. Proceedings of the Royal Society. 159 (B), 125-177. Morton, N.E., Crow, J.F& Muller, H..J.. 1956. An estimate ofthe mutational damage in man from data on consanguineous marriages. Proceedings of the National Academy of Science. 42, 855-863. Roberts, D.F. 1968. Genetic effects ofpopulation size reduction. Nature. 220, 1084-1088. Scbull, W.J. 1958. Empirical risks in consanguineous marriages; sex ratio, malformation and viability. American Journal of Human Genetics. 10,294-343. 7.4. Peeling. Cannings, C., Tbompson, E.A, & Skolnick, M.H. likelihoods on pedigrees ofarbitrary complexity. Adv. appl. 1976. Recursive deviation of 622-625. - 30Cannings, C~,Thomps()n,E~A, & Skolnick, M.H. 1978. Probability functions on complex.pedigrees. Adv. appl. Probab. lO,26-61. Elston, R.C., & Stewart, M.H. 1971. A general model for the genetic analysis of pedigree data. Human Heredity. 21,523-542. Lange, 1(., & Elston, R.C. 1975. Extensions to pedigree analysis I. Likelihood calculations for simple and complex pedigrees. Human Heredity. 23, lO5-112. Thomas, A. 1986. Optimal computation of Probability Functions for Pedigree Analysis. IMA Journal of Mathematics Applied in Medicine & Biology. 3, 167-178. 7.5. Other programs. Thomas, A.·· 1986. PEDPACK: An package of procedures for pedigree analysis. Technical Report Number 20, Department of Biophysics and Medical Computing, . University of Utah. ALG0L68C Thompson, E.A. 1977. Peeling programs for pedigrees of arbitrary complexity. Technical Report Number 6, Department of Biophysics and Medical Computing, University of Utah. Thompson, E.A. 1980. Package of recursive routines for computation on pedigrees. Technical Report Number 17, Department of Biophysics and Medical Computing, University of Utah. 7.6. Case studies. Bonne, B. 1963. The Samaritans: a demographic study. Human Biology. 35,61-89. ~Olds~rnidt, ~., Ro~en,A. &llo~eI1,I. 1960. Changirtg marriage systems in the Jewish communities ofIsrael. Annals of Human Genetics. 24,191-204. Roberts, D.F. 1971. The demography of Tristan da Cunha. 465-479. Population Studies. 25, Roberts, D.F. & Bonne, B. 1973. Reproduction and inbreeding among the Samaritans. Social Biology. 20, 64-70. Thompson, E.A. & Roberts, D.F. 1980. Kinship structures and heterozygosity on Tristan da Cunha. American Journal of Human Genetics. 32, 445-452.